Methoxy - hydroxy - amino benzene arsonic acid



Patented Nov. 21,. 193? UNITED STATES "PATEN T OFFICE METHOXY HYDROXY AMINO BENZENE ARSONIC ACID No Drawing. Application December 24, 1931", Serial No. 583,150, and in Germany January 3 Claims. (01. 260-14) The present invention relates to organic arsenic compounds, more particularly to com pounds of the following general'formula wherein one X represents the group AsOaHz, the other X represents hydrogen.

We have found that 1-methoxy-2-hydroxy-3- aminobenzene-arsonic acids can advantageously be used against protozoa diseases.

The new 1-methoxy-2-hydroXy-3-aminoben- .zene-arsonic acids can be obtained'by reducing the corresponding 1-methoxy-2-hydroxy-3-nitrobenzene-arsonic acids which may be prepared according to known methods.

The reduction of the l-rnethoxy-2-hydrcXy-3- ni'trobenzene-arsonic acids is preferably carried out by dissolving in water the acid in the form of an alkali salt, e. g. of its sodium salt, and adding sodium hydrosulfite to the solution thus obtained, By adding acetic acid, preferably glacial acetic acid, to this solution, the l-methoxy-Z-hydroxy- 3-aminobenzene-arsonic acid precipitates in the form of its sodium salt.

The new preparations are only slightly poisonousv when administered per 05, but they have quite a good therapeutic action. The dosis tolerata 'of,v for instance, 3-amino-4-hydroXy-5- methoxybenzene-l-arsonic acid per kilo of rabbit amounts to above 500 milligrams when administered per os. 25 milligrams will already cure the syphilis of rabbits, so that there is a chemotherapeutic index of more than 1/20. This could not be foreseen, since according to Berichte der deutschen cheinischen Gesellschait, volume 47, 1914, page 996, the CHso-group is distherapeutic and the 2-methoxy-4hydroxy-5-aminobenzenel-arsonic acid mentioned in Berichte der deutschen chemischen Gesellschaft, volume 48, 1915, pages 513 and 521, has no suitable action.

The following examples illustrate invention:

1. l-methoxy-Z-hydroxy-3-nitrobenZene-5-arsonic acid is obtained from 5-nitro-2-acetylaminoanisol by exchanging the acetylami'no group for hydroxyl, reducing the nitro group to the amino group, diazotizing the latter, substituting the arsonic acid radical for the diazo group and nitrating the 1-methoxy-2 hydroxybenzene-S-arsonic acid according to the following scheme:

. 17111000113 on 011 v 113cc H=c0- Baco- N02 N02 its,

1 on on -mco H3co N02 7 SOaHa ASOaHi 15 grams of the acid are dissolved in 150 cc. of

Water and 50 cc. of 10 N caustic soda solution. 35 grams of sodium hydrosulfite are added to the solution, While vividly stirring. The filtered solution is acidified With 31 cc. of glacial acetic acid, whereupon the 1methoxy-2-hydroxy-3-aminobenzene-S-arsonicacid separates in the form of its sodium salt. By dissolving in hydrochloric acid and neutralizing the solution thus obtained until the reaction to Congo paper is neutral, the free acid of the following formula:

AsOsHz formed is reduced with the calculated quantity of hydrosulfite to the amino-acid and then acetylated. By nitrating the 1 methoxy 2 acetylamino--arsonic acid, the l-methoxy-Z-acetylamino-3-nitrobenzenel-arsonic acid is obtained according to the following scheme;

NH.COCH3 l-arsonie acid. By nitrating this compound the nitro group enters the 2-position. The product is worked up to the l-methoxy-Z-hydroxy-3- aminobenzene-e-arsonic acid as indicated in the preceding examples.

We claim:

NHLCOCH;

H3CO- H300 H3CQ HsCO- N02 NH: AS03112 ASOaHz AS0 11 On treating this acid (10 grams) at C.- C. with strong caustic soda solution (20 cc. of caus tic soda solution of 45 Be. and 10 cc. of Water) there is split off at the same time the'acetyl group and ammonia with formation of 1-methoxy-2- hydroXy 3 nitrobenzene 4 -arsonic acid. The yield amounts to about 70% of the theory. By reducing by means of hydrosulfite, the l-methoxy 2 -hydroxy 3 aminobenzene-4-arsonic acid of the following formula:

-H3 0 O N 2 ASOaHz is obtained. It is soluble in alkali, mineral acids, Water and methyl alcohol.

3. The 1 -methoXy-2-hydroxy-3-aminobenbene 4-arsonic acid can also be prepared by starting from 1 -methoXy-2 acetylaminobenzene. This compound is nitrated, reduced, diazotized and caused in the usual manner to react with arsenious acid to produce 1-methoxy-2-acetylamino- 1. The compounds of the following formula 1130 0- NHZ 

